Natural environments, ancestral diets, and microbial ecology

21 Pages·2015·1.37 MB·English

by  Alan C Logan

Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9
DOI10.1186/s40101-014-0040-4
REVIEW Open Access
Natural environments, ancestral diets, and
microbial ecology: is there a modern
“ ”
paleo-deficit disorder ? Part II
Alan C Logan1*, Martin A Katzman2 and Vicent Balanzá-Martínez3
Abstract
Famed microbiologist René J. Dubos (1901–1982) was an early pioneer in the developmental origins of health and
disease (DOHaD) construct.Inthe1960s, he conducted groundbreaking research concerningthe ways in which
early-life experience with nutrition, microbiota, stress, and other environmentalvariablescould influence later-life
health outcomes.He recognized the co-evolutionary relationshipbetween microbiota and the human host. Almost
2decades before the hygiene hypothesis,he suggested that children in developed nations were becoming too
sanitized (vs. our ancestral past)and that scientists should determine whether thechildhood environment should
be “dirtied up ina controlled manner.” He alsoargued that oft-celebrated growth chart increases via changes in the
global food supply and dietary patternsshould not be equatedto quality oflife and mental health. Here inthe
second part of our review, we reflectthewords of Dubos offcontemporary research findings in the areas of diet,
thegut-brain-axis (microbiota and anxiety and depression) and microbialecology. Finally, we argue, as Dubos did
40 years ago, thatresearchers should more closelyexamine therelevancyof silo-sequestered, reductionist findings
inthelargerpictureofhumanqualityoflife.Inthecontextofglobalclimatechangeandtheepidemiologicaltransition,
anallergyepidemicandpsychosocialstress,ourreviewsuggeststhatdiscussionsofnaturalenvironments,urbanization,
biodiversity,microbiota,nutrition,andmentalhealth,areoftenoneinthesame.
and stressesinthe variousmanifestations oflife…
“But it can be surmised that the consumption of new when,and if,we reach theproperlevelofknowledge,
kinds of food will bring in its train new types of nutrition willbecomepartof anewscience,asyet
medical problems. Nutritional disease can arise not undeveloped,human ecology”[2].
only from qualitative or quantitative deficiencies,
but also from toxic effects, which are often slow in Outside of his focus on the relationship between nutri-
manifesting themselves…scientific knowledge is not tionandintestinal microbiota, whichwewilldiscusslater,
yet sufficient to replace the biological wisdom Dubos did not write extensively on nutritional matters.
derived from the countless centuries during which Still, as evidenced from the quotes above, his broad view
mankind has engaged in the empirical trial of ofnutritionwasthroughthesameecologicalandancestral
foodstuffs” [1]. lens with which he surveyed other topics. However, and
thisisasalientpoint,hedidnotadvocateforsometypeof
“Inmyjudgmentwe are abouttoenteradifferent universal Stone Age cuisine. He scoffed at such notions,
phaseofnutritional sciences.Onebasedonfunctional stating that “unfortunately for clinical nutritionists (but
testsdetermining theroleof foodnotonly ingrowth fortunately for the human species), people can remain
and disease,butinthe variousfunctionswhichenable healthy and can function effectively on a great diversity of
thebodyand mind torespondeffectively tochallenges dietary regimens that are far different from those consid-
eredscientificallyideal”[3].
*Correspondence:[email protected]
1CAMNR,23679CalabasasRoadSuite542,Calabasas,CA91302,USA
Fulllistofauthorinformationisavailableattheendofthearticle
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Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page2of21
Modern research has certainly supported his pos- linkedwithmanyfavorablehealthoutcomes[13-15].De-
ition. Depending on their residential environment, our tailed analysis of the mid-Victorian period reveals that
hunter-gatherer ancestors sustained themselves using for a very brief period in United Kingdom history, an
an enormous variety of foods [4-6]. Indeed, the re- ideal combination of the best of ancestral diets and high
markable dietary flexibility exhibited by our ancestors levels of physical activity culminated in remarkable life
seems responsible for the success and expansion of the expectancy(beyondinfancy)andabsenceofdegenerative
genus Homo [7]. Interestingly, the modernized global disease [16]. However, by 1880, the era of processed,
food supply pushes homogeneity such that the diversity high-sugar,andlow-nutrientfoods began.
of crops contributing to worldwide nutrition, including Recent advances in the field of nutritional psychiatry
starchy roots, has declined [8]. Regardless of the car- havemadeitclearthatthereareindeedremarkableways
toonish “rack of ribs” stereotypes, ancestral diets are inwhichnutritioninfluencesbrainstructureandfunction,
united in what they included (plants) and what they did aswellasmentalhealthandcognition[11,17].Evenshort-
notinclude(ultra-processedfoods). term adoption of traditional dietary patterns can benefi-
Food consumption and household food expenditure cially influence mood and cognition [18]. An increasing
trends in Canada (1938–2011) present a clear picture of number of epidemiological studies, including several that
thedietary shift inthelastcentury.Unprocessed ormin- have followed subjects over time, have linked adherence
imally processed roots and tubers as a contribution to to traditional dietary patterns with lowered risk of de-
household caloric intake have declined by 80%. On the pressivesymptoms,anxiety,andmaintenanceofacademic
other hand, the consumption of ready-to-consume proc- progress [19-25]. Meat consumption, often painted with
essed and ultra-processed foods has more than doubled. the same brush (without considering processing) and vili-
Therehasbeena32%increaseinhouseholdfoodbudget fied without scientific justification [26,27], has been asso-
share devoted to ready-to-eat processed and ultra- ciated with lower risk of depression [28,29], and meat
processed foods. The largest jumps have been in proc- abstinence has been linked with higher risk of mental
essed meats, sweetened beverages, spreads and sauces health disorder [30]. This is not to suggest that meat is a
(including mayonnaise- and margarine-containing prod- mental health panacea; a strict plant-based diet, lower in
ucts), and sweetened baked goods [9]. At the same sweets and rich in fruits and vegetables, may alsosupport
time, the latest research shows that Canadian adults positivementalhealth[31].
(age 19–50) consume only 0.5 servings of dark green Connections between nutrition and mental health
vegetables and 74% of the population aged 2 and older extend to mortality. For example, those with a lifetime
were not meeting Health Canada’s guidelines for fruit history of attempted suicide have been reported to
andvegetableintake[10]. consume significantly less meat, fruits, and vegetables
Duringhistimeofwriting,“propernutrition”wasbeing [32]. On the other hand, healthy dietary patterns charac-
celebrated for causing rapid gains in height and weight terized byhigherintake of vegetables, fruits, potatoes, soy
of populations such as the Japanese. Dubos discussed products, mushrooms, seaweed, and fish are associated
the associations between a 15-fold increase in milk with a decreased risk of suicide [33]. The developmental
consumption (plus 7.5-fold increase in egg and meat originsofhealthanddisease(DOHaD)constructprovides
consumption—1950–1975) and marked Japanese growth clear evidence that early life is a critical time in subse-
chart increases; however, he did not equate increasing quent risk of non-communicable diseases [34,35]. With
height with quality of life. As he said, “the post-war his groundbreaking studies on the long-lasting effects of
Japanese are taller than their parents, but this doesnot environmental variables experienced in early life, Dubos
mean they will live longer, will be happier or will be- helped to place DOHaD under the scientific microscope
comemoreproductiveintheartsandsciences”[2]. [36]. Today, pre- and post-natal nutrition is now being
He urged scientists to examine the behavioral aspects clearly linked to later mental health outcomes and child-
of nutrition, to more closely evaluate the ways in which hoodnutritionwithacademicperformance[37-39].
nutritionallowsanorganismtomakeadequate“biological Specific components of traditional dietary patterns,
and psychological responses to various life situations” [2]. including, but not limited to cocoa polyphenols, green
Heencouragedtheuseofobjectivemarkerswhereverpos- tea, coffee, grapes, and various spices, have also been
sible. Moreover, Dubos argued for research into the ways linked to positive mood, cognitive efficiency, and a de-
in which psychological distress and disturbances in circa- creased risk of depressive symptoms [40-46]. Experi-
dian rhythms can influence the metabolic demands for, mental research shows that the phytochemicals found
andfateof,variousnutrients[3]—topicsthatonlyrecently within traditional foods (e.g., tea polyphenols and resvera-
havebecomethesubjectofscientificscrutiny[11,12]. trol)andomega-3fatsthatarerelativelymoreabundantin
Adherence to ancestral dietary patterns, exemplified fish and free-range meats can influence brain function via
by the Mediterranean or Paleolithic descriptive, has been neurotransmitter availability for synaptic communication
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page3of21
[47-49]. They can also increase the production of neuro- consideration. Personal experience with the growth of
trophicfactorsresponsibleforneuronalstructureandfunc- edible plants (through residential-, community-, and/or
tion[50-52].Theevolutionaryadvantageofphytochemicals school-based gardening) and the subsequent promotion
tobothplantsandhumanshasbeenpostulated[53]. of healthy dietary choices is yet another [71,72]. How-
When humans encounter psychological stress, they ever,onemalleabledimensionofpersonality—conscien-
often turn to calorie-dense, nutritionally poor “comfort tiousness—may also represent a more specific point of
foods” [54-56]. In otherwise healthy adults, wherein intersection.
negative mood state is experimentally induced by re- It is now widely recognized that personality trait
searchers, the direct infusion of fatty acids in the stom- changes are commonplace in adulthood; conscien-
ach (therefore bypassing olfactory, visual, and gustatory tiousness is one of the major dimensions of personality
cues) can quickly rectify the lowered mood state [57]. that can undergo remarkable change in the period be-
As much as phytochemicals may protect us, are there tween adolescence and midlife [73]. Increases in con-
evolutionary factors that might lead modern humans scientiousness during adulthood predict improved
away from traditional dietary practices? Does fast food mental and physical health over time [74]. Moreover,
create a dependence? It would make sense that in our increases in conscientiousness during the influential
Paleolithic past, heightened pleasure associated with agesof13–21appeartoplaceyoungadultsonatrajec-
energy-dense food consumption would further motivate tory toward higher prosocial behaviors later on [75].
intake—a critical motivation given the frequency with Individuals scoring high on conscientiousness appraise
whichfoodscouldbecomescarce. natural environments as highly relevant for their emo-
The preponderance of epidemiological and experimen- tional well-being [76]. They are also more likely to
tal research indicates that the highly palatable addition choosehealthyfoods[77,78].
or relative magnification of sugar, fat, and/or sodium Theavailable evidenceprovidesa soundargumentthat
contributes to the attractiveness of the contemporary engaging in healthy behaviors can increase conscien-
ultra-processed diet [58-62]. Animal models of early-life tiousness [79]; in turn, the rewards associated with a
stress demonstrate that the Westernized diet can specific lifestyle habit, e.g., physical activity or cognitive
minimize the physiological stress response, supporting restoration in a natural environment, may motivate an
the notion that consumption of palatable foods is a individual to broaden the scope of behaviors associated
form of “self-medication” [63]. Moreover, the perinatal with conscientiousness. This speculation will require re-
period represents a highly sensitive period in which search validation; however, researchers are beginning to
dietary experience may dictate subsequent food prefer- track the ways in which day-to-day positive affect, feel-
ences and mental outlook over the offspring life course ingsofengagement,purpose,andmeaninginlife,aswell
[64,65]. For example, perinatal experience with a high-fat as curiosity and creativity, interact with dietary choices
dietinanimalsincreasesthelikelihoodofanxietybehavior intheshortandlong term[80,81].
and the expression of corticosterone receptors in the Of course, there is also the obvious dilemma related to
amygdala in adulthood [66]. Taken together, the physio- the ways in which income-driven increases in global food
logical responses to the consumption of energy-dense demand are connected to environmental degradation and
comfort foods are likely to be behaviorally reinforced in biodiversityloss.Theconsequencesofclearingofsavannas,
thecontemporaryenvironmentwhereinpsychologicaldis- grasslands, and tropical forests to accommodate a palate
tressandcognitiveloadarehigh. thatisincreasinglyfondofWesternizedfarerequireurgent
Although tempting to dismiss the mental health value researchattention.Ifcertaindietarypatternsareconnected
oftraditional diets as largely unrelated tothose of natural to the promotion of mental health, how would such diets
environments, there are multiple points at which the differintheirimpactonenvironmentaldegradation?
discussions become potentially one in the same. Closer At least one landmark study has initiated much-needed
residential proximity to urban green space is associated dialogue [82]. If urbanization and income increases con-
with healthier dietary habits and lower insulin resistance tinue on their current trajectory, by 2050, the global shift
[67,68].Intraditionalcommunities,suchasinMalawi,the in dietary pattern will be as follows: 15% more calories,
loss of forest cover is associated with diminished dietary 11% more protein, 61% more calories in non-nutritive
diversityandanincreasedriskofnutritionalgaps[69]. foods and beverages, 23% more pork and poultry, and
At the top level, the ability of natural environments 31% more beef and ruminant meat, 58% more dairy/eggs,
(or images of natural environments) to mitigate cogni- andastaggering82%morefishandseafood.Ontheother
tive load, discounting, and impulsivity in a contempor- hand,therewouldbean18%decreaseinservingsoffruits
aryenvironment—where these forces, along with screen and vegetables and a 2.7% decline in plant protein intake.
time, advertizing and other marketing forces can drive Moreover,therewouldbea32%increaseindietary-driven
unhealthy dietary choices [70]—is an obvious area of greenhousegasemissions.
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page4of21
However, in comparison to projections of the current page 7 “Therefore, he suggested that science
global average diet, the global adoption of more trad- should decide to expose the young to a wide
itional dietary patterns through 2050 painted a different variety of the ever-present microbes to
picture in health outcomes and the environment. Using build up tolerance….”
an average of three modeled traditional diets—the Medi-
terranean diet, a vegetarian diet, and a pescetarian diet In 1973, Dubos floated a bold suggestion during his
(vegetarian diet that allows fish/seafood)—there would keynoteaddresstotheMilwaukeeAcademyofMedicine.
be a 43% reduction in GHG emissions compared to the He cautioned, presumably to the astonishment of many
current standardglobalaveragediet.Inaddition,aneven in the audience, that North American children were
combination of these three more traditional diets would being over-sanitized, and an associated loss of tolerance
require, on average, 540 million hectares less in land wasnotwithoutconsequence.Asstatedinthenewspaper
demand vs. the current standard global average. The reportcitedabove,hiscontentionwascertainlynotinline
modeling showed, unsurprisingly, that there would be a with any mainstream thought circa early 1970s. This was
reduction in major non-communicable disease (NCD) the dawning of the era of the sanitizing-product industry
risk accompanied by a transition to more traditional (antimicrobial consumer goods were already a 1-billion
diets[82]. USDindustryin1966[86]).
It should bepointed out that the Mediterranean diet is His address was 16 years before the publication of the
a broad term. From an ancestral perspective, there are so-called “hygiene hypothesis,” which suggested that the
many regional and local differences in food availability, global rise in allergic disease could be related to dimin-
as well as culturally determined influences on compo- ished opportunity for early-life exposure to pathogenic
nents such as meat content [83]. Within Italy, research microbe exposure via increased hygiene, antibiotics, and
suggests that high adherence to a Mediterranean-style smaller family sizes [87]. It was decades before Swedish
diet equates to about 30% less meat intake vs. adults physician Agnes Wold proposed a more general gut
who maintain a low adherence to the traditional pattern microbial deprivation hypothesis, one that included “low
[84]. Although the 2050 projection research above exposure to bacteria via food or the environment in gen-
does not highlight diets that are the most effective at eral. All this results in an ‘abnormally’stable microflora”
promoting mental health, nor are the three dietary in Westernized nations [88]. It was decades before the
patterns called out by the researchers necessarily the immune-modulating properties of non-pathogenic mi-
most sustainable, it provides a home base to begin crobes would be scientifically postulated to be of value in
complex discussions. How to feed a global population neuro-emotional health (a proposition in which Dubos
quality nutrition that promotes health, lowers NCD wasreferenced)[89].
risk, and places the least amount of burden on natural Scientific consideration of exposing the young to a
environments? wide variety of bacteria, as Dubos proposed, is essen-
tially the cornerstone of ongoing research under the
Microbial ecology “biodiversity hypothesis” realm. The biodiversity hy-
“Washing May Be Harmful, Kids” Milwaukee Journal, pothesis has combined the more narrow hygiene and
Wednesday January 17th, 1973: report from the Annual gut microbial deprivation hypotheses into a wider
Meeting of the Milwaukee Academy of Medicine [85], scopethatincludesthecrisisofglobalbiodiversityloss;
page1. the broad view includes the ways in which diminished
He [Dr René Dubos] suggested that overzealous contact with natural environments and loss of total
sanitary efforts, a “lack of contact with the thousands of biodiversity (including microbes) intersects with human
usually innocuousmicrobesinthe outsideenvironment,” health[90].
might compromise the normal development of the im- Co-evolutionary discussions of microbes and humans,
mune system. He argued that for normal development so common today, are also an extension of what Dubos
and protection throughout life, to build up tolerance to had proposed. He is credited with this, not by the
harmful agents, a child’s environment be dirtied up in a present authors,butbyhis ownpeers writing intheNew
controlled manner. Furthermore, he said that a lack of England Journal of Medicine (1973)—“The term autoch-
contact with the thousands of usually innocuous mi- thonous has been applied to certain constituents of the
crobes in the outside environment at birth could retard flora by Dubos to indicate that the recent evolutionary
the development of the newborn’s defense mechanisms. development of these bacteria has been in concert with
Dubos acknowledged that his suggestions were not in that of the host.” Further,citingtheworkofDubos,itwas
line with contemporary thinking and that he “probably queried whether “the intestinal microflora might be
would not live long enough to find out whether he was regarded as an organ of the body, the proper function of
right.” which, like that of other organs, might be related to
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page5of21
optimal health?” [91]. If evolutionary co-development transcendsanalytical biologyandreaches intothe very
broughtabouttheexistenceofanorgan(microbiota),and philosophyof life”[102].
that organ interacts with other organs, the brain would
surelynotbeexcludedfromthemix. and
The concerns of Dubos regarding the increasingly
sanitizedworld,althoughspeculative,werenotbasedon “Manyother protectivemechanismsinvolving the
mere opinion. Despite becoming a scientific generalist, participation ofthenormal microbesofthebodywill
hewasfirstandforemostamicrobiologist.Hebeganhis certainlycometolight asattention isfocused onthe
career by discovering an antibiotic; however, he made it problem.”
clear early on that it was a potentially dangerous prac-
tice to tinker with microbial ecology. In his landmark, “Thedifficultiesthat mayfollow antibacterialtherapy
originalresearchpaperwithphysicianRussellSchaedler, areinfact similar inessence tothoseencountered in
entitled “The Digestive Tract as an Ecosystem” (1964), any attempttocontrolpredatorsinnature..Whether
theyquote themethod oftreatment affectsanimalpredatorsin
thewildernessorthebacteriainthegut,itisalways
“Thus,thecompositionofthemicrobialflora,which riskytotamperwith thenaturalbalance offorcesin
dependsupon environmentalandinternalfactors,in nature”[103].
turndeterminesthekindof biologicallyactive
substanceswhicharereleasedfromthedigestive tract Throughout the 1960s, Dubos was involved in a
into generalcirculation…thedifferent partsofthe series of studies related to DOHaD, including those
digestive tract,themicroorganismswhichitharbors, with germ- or specific-pathogen-free animals housed
and theconditions whichgovern theinterplaybetween in sanitary conditions. He also accumulated detailed
these variouscomponents,thus constitute ahighly analysis of the ways in which the normal intestinal
integratedecosystem.Anychangeinanyoneofthese microbiota could be disturbedand associatedthe changes
componentsislikely toaffecttheequilibriumand to various aspects of health. In addition, Dubos and col-
functionsofthe system asawhole,and thustohave leagues discovered ground-breaking interactions between
generalized physiologicaleffects”[92]. nutrition, psychological stress, infections, and the intes-
tinalmicrobiota[104-109].Inasummarythatmightseem
It is very unlikely that Dubos would be surprised with lifted from a recent newsworthy scientific publication
the recent discoveries indicating that microbes extend a circa2014,Dubossummarizedsomeof hisworkonthese
massive reach: from atmospheric chemistry and cloud intestinalmicrobiotainteractionshalfacenturyago—
formation [93,94], to mate selection and the remarkable
ways in which plants and soil microbes interact to deter- “Theimplicationsofthesefindingsaremany. For
mine growth characteristics and even insect feeding be- example,theycompelareinterpretationof the
haviors upon the plant, microbes matter [95-97]. Had he meaningofnutritionalrequirementsofanimalsand
lived long enough to see the dismantling of common men; theyalsoraisenewproblemswith regardto
myths, such as those which presumed bodily compart- factorswhichconditionresistancetomicrobialdisease.
ments such as the female womb during pregnancy is Itisclearthatmanycharacteristicsassumed tobe
sterile [98], that the vascular endothelium and subepi- inherentinanindividual caninrealitybedetermined
dermal regions are sterile in healthy adults, or that soil/ bythemicrobialfloraoftheintestinaltract”[110].
water-derived microbes cannot be found in the brain in
theabsenceofsignificantimmunosupressionand/ortissue Human research has recently made connections be-
destruction [99,100], he probably would not be surprised. tween greater diversity of intestinal microbiota, low-
Although the microbial contribution to general ecology ered markers of inflammation, and greater adherence
has been historically and grossly overlooked [101], Dubos to traditional dietary patterns [111]. Human research
wascognizantoftheconnection: has connected predominant bacterial phyla in the gut
with epigenetic regulation [112]. International studies
“Interms ofthetotaleconomyofnature,thecreative have linked urban residence with higher levels of in-
associationsinwhichmicrobes areinvolved are flammatory markers such as C-reactive protein among
probablyfarmoreimportantthan arethediseases adults [113-115]. There are likely many undetermined
that theycause,orthan thepracticalusesthat man ways in which psychosocial and environmental stressors,
makesofthem.Indeed,theentirelynewcreative some thatmaybe uniquetourbanenvironments, can ex-
processesthatthese associationsrepresentgivetothe plain these connections [116]. Interestingly, the early ori-
phenomenon of symbiosis a significancewhich gins of later-life inflammation have been the subject of
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page6of21
some research, with results indicating that exposure to allergy, the reader is referred to detailed and well-written
microbialdiversityduringinfancyisassociatedwithlower reviews [137,138]. The implications of this detrimental
CRPinadulthood[117]. synergy are not restricted to allergy and autoimmunity
The use of 16 s rRNA sequencing techniques has ad- [35].
dressedmanyofthelimitationsofstoolculturemethods. Antibiotic-induced changes in gut microbiota seem to
Researchers have found that, at least in Westernized place a higher burden of oxidative stress on an animal
urban dwellers, the slow differentiation of gut microbial [139]. Researchers are also connecting gut microbial di-
diversity relative to our non-human ancestors—one that versity (or loss thereof), antibiotics, and antimicrobial
occurred over millions of years—appears to be undergo- agents (e.g., triclosan) with obesity [140,141]. Experi-
ing a dramatic acceleration [118]. The advances in la- mental studies show that early-life low-dose antibiotic
boratory technique have shown that diet is a player in inducesmetabolicalterationsandinfluencestheexpres-
gut microbial diversity and that ancestral diets are more sionofgenesinvolvedin immunity.Low-doseantibiotic
aligned with an intestinal microbiota profile distinct alsoenhancestheeffectof high-fatdietinducedobesity.
from that linked to chronic illness [119]. The examin- These changes are transferrable to germ-free animals
ation of well-preserved ancient human coprolites (also when low-dose antibiotic-associated microbiotaare trans-
known as paleo-stool) shows that the microbiota profile planted,indicatingacausalrolefordysbiosis[142].
reflects ancestral dietary practices and culture, and its The critical point in the preceding research is that
broad composition more closely resembles that of a these results are noted with low-dose and subtherapeutic
modern hunter-gatherer vs. a Westernized urban resi- antibiotics, which raises multiple questions concerning
dent[120,121]. broad environmental sources of antimicrobials. Residual
Unsurprisingly, hunter-gatherers and other rural levels of antimicrobials in the global food supply are
dwellers in Africa and South America have higher now a significant concern to researchers [143-145].
levels of microbial richness and diversity [122-125]. Strong marketing forces push the commercially lucra-
Approximately 35% of all lactic acid bacteria isolated tive, yet very false notion, that our bodies and the sur-
from raw fruits and vegetables survive gastric conditions, faces with which we make contact must be routinely
and the diversity and functionality of microbiota of trad- cleansed of all microbial life [146]. Given that 45% or
itional/indigenous foods and beverages is far more com- more of neonates are exposed to antibiotics in North
plex than previously realized [126,127]. Remarkably, the America [147], and emerging links between this exposure
gutmicrobiomeappearstoco-evolvewithregionaldietary in infancy and subsequent overweight status through
patterns (and specific foods within them) via horizontal childhood [148,149], the urgency with which this topic
gene transfer from extrinsic microbes that allow for the needstobeaddressedisnowobvious.
breakdown of novel carbohydrates [128]. Further still, Other remarkable diet-microbe connections are emer-
there are uncanny functional resemblances between plant ging.Therapidappearanceofultra-processed,ready-to-eat
rootandhumanintestinalmicrobiotathatmaybeofevo- foods may be increasing our intake of advanced glycation
lutionarysignificance[129]. end (AGE) products within those foods [150]. AGE are
Inordertoexert theirfar-reachingphysiologicaleffects, highly oxidant compounds formed through the non-
beneficial microbes need not become part of the estab- enzymatic reaction between reducing sugars and free
lished residential intestinal microbiota—nor do they have amino acids and are much higher in foods prepared with
to be live. For example, in a recent experimental study, hightemperatureintheabsenceofwater.AGEhavebeen
intakeofaheat-killedstrainofLactobacillusbrevishad shown toreducethegrowth of beneficialmicrobes inhu-
a beneficial influence on circadian locomotion and man and animal samples [151]. Higher intakes of dietary
sleep rhythms [130]. With emerging research showing AGE are associated with a decline in cognitive function
that mere fragments of microbes (e.g., microbial DNA [152].
vs. live viable bacteria) can signal pathways, including Agents such as non-nutritive sweeteners have been
the production of inflammatory-mediating cytokines shown to inhibit the growth of bacteria, diminish intes-
[131-133], it is clear that we are merely scratching the tinal microbial diversity, and encourage fat accumulation
surfaceoffunctionality. andglucoseintoleranceinexperimentalstudies[153-156].
As mentioned in the Part I introduction, the combin- Environmental pollutants in air and food have also been
ation of Westernized dietary patterns and increasing mi- shown to cause significant changes in gut microbiota
crobial sanitization (antibiotic/antimicrobial product use) [157,158]. On the other hand, the ability of select non-
mayplayasynergisticroleinrelationtomarkedincreases pathogenic microbes to assist in the elimination of envir-
in allergic and autoimmune conditions in developed na- onmental toxins from the body of mammals is becoming
tions [134-136]. For further discussion on these relation- more obvious [159,160]. These findings, as well as others
ships,andwhathasbeendescribedasaglobalepidemicof related to allergy and obesity research, should not stand
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page7of21
alone. They are clearly intertwined with other silos, in- differences in ancestral evolutionary development are
cluding broad discussions of mental health and the emer- reflected in the presence or absence of members within
ging research surrounding a microbiome and mental the indigenous microbiota of various species. As usual,
healthconnection[161]. he demonstrated his awareness of socio-ecological inter-
playinhumans:
Hygiene, allergy, and mental health
In 1972, Dubos reported that when female specific- “Whatevertheexact mechanismoftheinterplay
pathogen-free mice are fed low-quality protein during between nutritional state andthemicrobiotaofthe
the perinatal period, the brain content of dopamine and digestive tract,itisclearthat rateof growth,
norepinephrine in offspring is diminished [162]. In 1986, nutritionalrequirements,andefficiency infood
Linda Hegstrand and colleague R. Jean Hine reported a utilizationarecharacteristicsinfluencedby
remarkable discovery to the scientific community—com- [commensalbacteria]…But sanitarypractices and
pared togerm-free animals, conventionally raised animals otheraspectsofthewaysoflifemayalsoplay an
havehigherlevelsofhistamineinthehypothalamus[163]. importantpartbyaffecting theindigenous
While best known for its connection to allergy, brain his- microbiota…histologicaldifferencesobservedinthe
tamineingeneral,andhypothalamichistamineinparticu- intestinalmucosa dependingupon the socioeconomical
lar, is a key factor in arousal and behavior [164]. Perhaps status maybe relevanttotheproblem,sincethey
underappreciated at the time, their work was a milestone probablyreflect theintensityoftheinflammatory
inthegutmicrobiota-to-brainaxis. responsetothe so-called‘normal’flora.”[167].
Although the hygiene hypothesis itself remained fo-
cused in the realm of allergy, it was proposed in 2002 Fast-forward and studies using germ- and pathogen-
that the ways in which beneficial bacteria influence T- free mice have shown definitively that microbes can in-
helper cells (TH1:TH2 balance) in allergies might also fluence brain and behavior [168,169]. In one of the
extend to conditions where neurocognitive symptoms most remarkable experimental studies to date, the
are common. When this seemingly outlandish proposal transplantation of fecal microbiota from donor mice
was made (accepted Aug, 2002), it was pointed out that raised on a high-fat diet into lean mice (who had been
allergies are a frequent overlap with chronic conditions raised on a normal chow diet) resulted in altered
in which emotional and somatic symptoms are a central neurologicfunction.Specifically,therewere changesin
feature. If TH1:TH2 imbalance was a driver of many behavior suggestive of anxiety, increased stereotypical
emotional and somatic symptoms, then a mitigating role behavioranddecreasedmemory[170].
forbeneficial microbeswastheoreticallypossible [89]. These studies show us that microbes matter; however,
As the traditional focus on harmful microbes began to there are massive limitations when using rodent studies
shift toward lactic acid bacterium and commensals, as a means to provide translation in general [171] and
novel scientific frameworks began to bridge the im- especially toward complex issues such as mental health
mune/nervous systems to neuropsychiatric health via [172-174]. How far can we carry the clinical relevancy of
non-pathogenic microbes and nutrition. Although in germ-free rodents and/or elevated plus mazes used to
the early 2000s, these discussions were forced to the measure rodent “anxiety” vis-à-vis the equally complex
fringes, far removed from the safety net of the impending human ecosystem? Animals in the natural environment
microbiome frenzy, Dubos was not overlooked in the ref- might experience dysbiosis—but they are not living la
erence lists [89,165]. Over the last decade, experimental vida germ-free. Although Dubos put DOHaD on the
and preliminary clinical studies have produced findings map with his own germ- and pathogen-free rodent stud-
that would have been virtually inconceivable to most at ies 50 years ago, he would almost certainly agree with a
the end of the 20th century. Strangely, Dubos has an ap- criticalnote concerningglobalmentalhealth—psychiatry
pallingly low number of citations (to what should have isnotappliedneuroscience[175].
beenmilestonepapers—e.g.,[162])onGoogleScholar. This sometimes inconvenient yet perspective-providing
Concerning his own groundbreaking studies on the factcan,attimes,beeasilyoverlooked.Whilemanyfuture
microbiota of the total environment and what it might promissorynotesarenowbeingsignedoffwiththesigna-
mean to human well-being, Dubos referred to himself as tureof“microbiome,”Duboswarnedaboutselectoversell-
simply walking in Metchnikoff’s footsteps [166]. Within ing of similar technological advances in his time. He
his book Man Adapting (Yale University Press, 1965), he referred to their promotion at scientific meetings as a
details his own experiments on fecal microbiota trans- combination of “intellectual dishonesty” and “intellectual
plantation and immunity. He found that a more sani- escapism”whentheyignoreglaringholisticenvironmental
tized environment reduced intestinal microbial diversity variables that are not nearly as press-release-worthy
in mice. In this remarkable text, he makes it clear that [176]. In the contemporary tweet-driven world of
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page8of21
pseudo-medico social media [177,178] and overhyping that make up the portions of the human skin and intes-
of research by academics [179], his concerns may be tinal microbiota such as Actinobacteria, Bacteroidetes,
particularlyrelevant. Firmicutes, and Proteobacteria. In particular, 16 s rRNA
Notwithstanding translation difficulties, the emerging sequences assigned to the lactic acid bacterial group are
rodent studies have provided some undeniably valuable higher in rural air [195]. A 4-day, 3-night trip to a forest
clues to possible mechanistic pathways between microbes setting has been associated with a significant reduction of
and brain function. Collectively, the experimental studies serum levels of the TH2 chemokine MDC/CCL22 [196],
indicate that beneficial microbes might influence neu- whichallowsforspeculationconcerningmicrobialmecha-
rocognitive function, behavior, and perceived stress by nismsofaction.
various pathways: direct communication to the central The results of a recent European studies provide con-
nervous system (most likely via the vagus nerve), con- textual meaning to the public health implications of bio-
trolling the intestinal barrier (and limiting systemic diversity loss at the microbial level. Lowerbiodiversityof
low-grade inflammation), improvement of nutritional vegetation surrounding one’s residence has been associ-
status(phytochemicalabsorptionandneurotransmitter ated with higher odds of an allergic IgE reaction to com-
precursors), reducing systemic oxidative stress, regulation mon allergens and lower diversity of select bacteria on
ofglucosecontrol,andlimitationofuremictoxinproduc- the skin [197]. In fact, the extent to which green areas
tion[180-183].Undoubtedly,otherswillberevealed. (within 2–5 km from primary residence) are inversely
In the clinical setting, several studies have shown that associated with atopic sensitization in children may be a
oral probiotics, or fermented foods/beverages inclusive product of the way these natural environments differen-
of beneficial bacteria, may provide value in end points tially shape commensalskinbacteria[198].
such as depression, anger, anxiety, and daily mood It seems likely that this is the type of research with
[184-189]. Perhaps the most interesting study to date which Dubos would have been most impressed. Reduc-
involved functional magnetic resonance imaging (fMRI) tionist technique immediately provides clear relevance
assessments before and after the 1-month consumption to the broad environment. Since these environmentally
of a microbial-fermented vs. unfermented food—with influenced skinmicrobes,membersoftheGammaproteo-
imaging results suggesting a reduction in vigilance to bacteria family, in particular, can influence the immune
negative environmental stimuli among the healthy adults system beyond the skin itself [199], similar relationships
that consumed the fermented dairy product [190]. Re- maybefoundinconnectiontomentalhealth.
search has also identified intestinal microbiota differences
in those with major depressive disorder and chronic fa- Outdoor activity and microbiota
tigue [191,192]. On the other hand, numerous studies A number of academic articles have concluded that
showthatthosewithdepressivesymptomsandhighlevels modern humans would do well to exercise in ways that
of psychological distress engage in dietary patterns that reflect our hunting and gathering past [200,201]. Indeed,
are far removed from a healthy traditional pattern that physical activity in natural environments may increase a
mightotherwisesupportmicrobialdiversity[11]. sense of vitality and motivate an individual to adhere to
future exercise routines [202,203]. This is of particular
Beyond food and probiotics importance in those with mental health disorders or
While intestinal microbiota and dietary interactionshave obesity in whom motivation is a primary barrier to phys-
received considerable international attention, it is worth icalactivity[204].Commonsymptomsof mentaldisorder
noting that lactic acid bacteria, bifidobacteria, and nu- are predictiveofsubsequenttimespent sittinglater inlife
merous other potentially beneficial microbes are found [205]. Exercise feels differently for those who embrace it
throughout natural environments. For example, lactic as part of their lifestyle vs. individuals with depressive
acid bacteria make up a significant portion of the phyllo- symptoms or obesity—the latter groups report lower
sphere(theabovegroundbotanicalhabitatformicrobiota) pleasureratingsandpost-exerciseenergylevels,whiledur-
even under extreme conditions. Moreover, bifidobacteria ing the activity perceived exertion levels are higher
are found in the rhizosphere (narrow band of soil just [206,207]. Since fostering positive emotions in association
under the surface, associated with root secretions) of with the experience of exercise can alter the way exercise
some of the harshest environments on the planet Earth feelsandencouragefutureparticipation[208,209],theim-
[193,194]. plications for the value of natural environments are
Indeed, significant differences have been noted between obvious.
themicrobialcontentofurbanvs.ruralair—resultsshow- Beyondtheclassicallyknownbenefitsofphysicalactivity
ing greater overall diversity in the rural near-surface (cardiovascular, respiratory function, etc.), and the more
atmosphere. There is also relatively higher abundance of indirect sensory and psychological (mood, cognitive res-
bacteria in rural samples, including the microbial phyla toration,etc.)value,thereisathirddimensionofpotential
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page9of21
benefit related to outdoor activities. We consider the po- realm suggest that not all microbial strains are alike
tential diversity of microbial contact to be important and [183,223,224]. Are there strain-specific effects of M. vac-
often overlooked consideration. In addition to vegetation cae in neurocognition? If so, in what environments are
as mentioned above, outdoor air has a greater phylogen- thesestrainsmostabundant?Inourcontextofnaturalen-
etic diversity of bacterial communities than does indoor vironments,wewouldbeinterested toseeiftherearebe-
air[210]. havioral changes as a result of other non-commercially
Outdoor play, gardening, or any activity that might linked, non-pathogenic soil, or phyllosphere-associated
bring contact with soil, trees, and plant life will increase microbes.
the opportunity for exposure to microbial diversity. If
the activity is conducted in natural environments, it The total environment
increases the likelihood that the individual will inhale
natural phytoncides (aromatic chemicals secreted from “Icannot helpbutexpressingmybelief that living
trees and ornamental plants) that are associated with things,including man,respondnot onlytoheat,
human stress reduction and immune system benefits humidity,light andotherobviousclimatic components
[211,212]. These airborne phytoncides, found at higher whicharereadilyperceivedbythe senses,but alsoto
levels in natural (vs. urban built) environments, are a manyotherenvironmentalfactorsnotreadily
product of interactions between phyllospheric micro- identified,andinpart,stillunknown”[225].
biotaandtheplant;forexample,theapplicationofanti-
microbials to the aboveground portions of flowers leads Human biometeorology is an interdisciplinary science
to a halt in linalool emissions [213], a chemical with concerned with interactions between atmospheric pro-
knownmood-regulatingproperties[214]. cesses and living organisms. In the context of climate
Recently, it was reported that athletes who make fre- change and environmental degradation, this field has ex-
quent contact with natural grass, soil, and mud (Rugby perienced renewed interest [226]. Natural environments
players)havegreaterdiversityofgutmicrobiotavs.phys- can also be distinguished from the urban built environ-
ical size, age- and gender-matched controls [215]. The ment by some of these atmospheric differences. For ex-
fact that Rugby players engage in a unique form of exer- ample, trees may help mitigate the thermal discomfort
cise that brings them in direct contact with the Earth associated with urban heat island effects [227]. On the
was not mentioned by the authors—the conclusion was other hand, urban warming may encourage herbivorous
focused primarily on differences in exercise intensity. pestabundanceandtree destruction[228].
However, intestinal microbiota is not solely a product of One of the more controversial aspects of meteoro-
diet, and the influence of non-diet-associated terrestrial logical conditions astheyrelatetohealthoflivingorgan-
microbes on intestinal and systemic physiology is an isms is that concerning the relative content of charged
open question [216-218]. Undetermined environmental air ions. Dubos maintained an open mind on the topic.
factors that are unique to geographically distinct human Despite suggesting that air ions may have untold bene-
societies may even transcend the dietary influence on fits, including an ability to modify beneficial microbes
gut microbiota composition[219]. within the intestinal tract [167], page 124], Dubos took
The administration of live Mycobacterium vaccae has exceptiontoanyassociationbetweenhimandcommercial
recently been shown to improve cognition and reduce ion-generatingdevices[229].Unquestionably,theresearch
experimental signs of anxiety in an animal model [220]. related toairionshasbeenthesubjectofpseudo-medical
M. vaccae is a generally non-pathogenic microbe that, exploitation in marketing claims associated with ion-
depending on region, can be found in varying amounts generatingdevices.
within soil, mud, and/or natural water wells [221]. An However, since his writings on the topic, emerging re-
earlier 2004 study involving an injection of M. vaccae search is undoing the notion that air ions are without
(non-placebo-controlled) in patients with lung cancer any relevance to the growth and function of living or-
indicated that it may attenuate some aspects of deterior- ganisms. The preponderance of available evidence shows
ation in quality of life [222]. Media positioning of M. that air with a relative increase in negatively charged ions
vaccae as the “happy” widely available soil bacterium is mayhelpfacilitatepositivementaloutlook[230-232].The
common, and it may lose sight of the fact that this par- relative concentration of negatively charged air ions is
ticular microbe is associated with intellectual property higher in natural environments [233-235] and lower in
andalong listofpatents. urban(aswellasindoor)environmentsthataresubjectto
M. vaccae is often used as a broad term that does not airborne pollutants [236,237]. Forests and areas rich in
address its many specific strains. There has been little vegetation can help offset the loss of negatively charged
discussionsurroundingthespecificityofM.vaccaestrains air ions within urban environments [238]. Remarkably,
and emotional health; probiotic studies in the gut-brain negative air ions also appear to increase phytoncide
Loganetal.JournalofPhysiologicalAnthropology (2015) 34:9 Page10of21
release from trees [239], indicating the potential rela- we must underscore that not all global cities and dis-
tionshiptosomeofourpreviousdiscussions. tricts within cities can be painted with the same brush
In daily life and sleep, our ancestors would have made [252]. On a global scale, however, environmental injus-
muchmorefrequentdirectcontact withtheEarth. Some tices are common and the concentration of urban vege-
researchers have speculated that less frequent contact tation and biodiversity is often slanted in favor of the
with the surface of the Earth may translate to a affluent and less vulnerable [253-256]. Any slant away
deprivationincontactwithabundantsurfaceelectrons, from natural environments is not a zero-sum game. It
which in turn could impair diurnal electrical rhythms forcesaquestion:whatmightbethereinitsstead?
and burden the antioxidant defense system [240]. Only Lack of green space in urban environments, especially
properlydesignedstudiescandeterminewhetherthispar- in socioeconomically disadvantaged areas, is often coin-
ticularspeculationmayhavebroadhealthimplications. cident with more grey spaces. These are residential areas
Finally, a less speculative area of total environment re- with disproportionate industrial and commercial activity,
search is one touched upon in Part I—that of light. As heavy traffic, bars, liquor stores, convenience stores, and
mentionedpreviously,ourcurrentrelationshipwithlightis fast-food outlets [257-263]. Although these zones may
divergent from our ancestral past—higher levels of light at contain limited vegetation, there is an abundance of vis-
night(LAN)andlowerexposuretolightduringthedayare ual marketing of unhealthy lifestyle choices—e.g., fast
now commonplace. Here, we briefly mention the import- food andtobacco [260-262].
ance of the blue portion of the light spectrum. In a recent Therefore, many of the mental health benefits of green
NorthAmericanstudy,itwasreportedthatthedailyexpos- space may be explained top-line by the absence of grey
uretolightintensityabove1,000lux(levelsassociatedwith space—i.e. less noise, traffic, walkability, environmental
outdoorlight)wasonlyaboutanhouronaverage.Interest- toxins, and visible marketing that otherwise cajoles resi-
ingly,inthatstudy,thosewhoaccumulatedthemajorityof dents toward (and less actual opportunity to partake in)
their intense daily light exposure (levels beyond a 500-lux unhealthy lifestyle choices [11,264,265]. The financial
threshold) in the early part of the day were more likely to strain and fatigue associated with psychological distress
havealowerbodymassindex(BMI)[241].Whywouldget- in socioeconomically disadvantaged areas enhances the
tingoutdoorsinearlymorninglightmakeadifference? attractiveness of cost and convenience in low-nutrient
One possibility is the higher amounts of shorter wave food choices [11].Perhapstimespent indoorsmaynotbe
blue light in the early part of the day [242]. Given the completelydisadvantageousiftheexternalenvironmentis
emerging research on appropriately timed blue light ex- pollutedanddangerous.
posure and positive mental health [243], it appears to be Moreover, we must acknowledge that generalized
yet another feature of the total modern environment stress (and specific stressors—e.g., acoustic stress), pol-
that we may be missing, at least in the daytime. While lution, marketing toward junk food, smoking, antibiotic
our standard interior lighting cannot compensate for the prescriptions [266-270], and other socioeconomically
amount of blue light found in natural daylight [244], slanted environmental forces described above might
only a small amount of evening blue light can suppress continuously influence microbial diversity and dysbiosis
melatonin. The consequences of evening-night use of [11,157,158,271-273] unless they are addressed. This
modern interior lighting and multimedia screens (i.e., puts a dampener on the oft-unchecked enthusiasm with
higher blue light) may be compromised sleep, fatigue, which single (or a few) strains of isolated bacteria are
mood,andmetabolic disturbances[245-247]. heralded as a mental health solution. It is hard not to
Circadian disturbances have been shown to induce draw parallels between the microbiome euphoria of
dysbiosis in both mice and humans—and promote glu- today, and the emergent technological research Dubos
cose intolerance and obesity that are transferrable to addressedin1969:
germ-free mice upon fecal transplantation [248]. There-
fore, we have much to learn about the far-reaching ef- “Thisiswonderfullyentertaining,titillatingkindof
fects of light and its components. Dubos would probably sciencefiction.Weorganizemeetingsaboutitinallsorts
have been less interested in the clinical utility of various ofpleasantplacestotalkaboutthis,andthatsavesus
doses of melatonin to mediate jet lag and more inter- theresponsibilityofwalkingacrossthestreet,where
ested in its evolutionary origins [249] and the lifestyle 100,000childrenarebeingpoisonedeverydaybylead
drivers [250] behind why its use as a supplement has inpaint…somethingcanbedoneimmediatelyabout
dramaticallyincreasedindevelopednations[251]. thisproblem,butitisnotbeingdonebecauseitisnotof
sufficientinterestorasexcitingintellectually”[176].
Heterogeneity of cities, vulnerable populations
After weaving our way through each of our main sec- Putsimply,arewetoimagineaworldinwhichtheso-
tions—natural environments, nutrition, and microbes— cioeconomically disadvantaged line up for laboratory-